P1285: IMPROVING THE EFFECTIVENESS OF FIRST-LINE THERAPY FOR STAGE IV DIFFUSE LARGE B-CELL LYMPHOMA WITH UPFRONT AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION.
Authors: Aleksei Koviazin, Larisa Filatova, Ilya Zyuzgin, Anna Artemyeva, Ilia Poliatskin, Leonid Kramynin, Tatiana Semiglazova
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Improving the effectiveness of first-line therapy for diffuse large B-cell lymphoma (DLBCL), especially at high risk, remains an urgent clinical task of oncohematology. Upfront high-dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation (auto-HSCT) can be an effective option to increase the survival in these patients. Aims: To improve the effectiveness in first-line therapy stage IV DLBCL. Methods: A group of 105 patients(pts): DLBCL NOS, age 18-65, stage IV, IPI≥2, CR/PR after x6 R-CHOP/R-DA-EPOCH from 2010 to 2019 at NMRC of Oncology named after N.N. Petrov of MoH of Russia was retrospectively analyzed. The upfront group included patients with HDCT followed by auto-HSCT as a first-line consolidative therapy (n = 35). The control group included patients with follow-up after induction (n = 70) with CR only. Primary endpoint was 3-yr progression-free survival (PFS). Secondary endpoint was 3-yr overall survival (OS). Observation period: 60.6±22.4 mon in upfront vs 62.5±41.1 mon in control, p = 0.78. Double-expressor lymphomas (DEL) had equal distribution – 37% (13/35) pts from upfront group and in 40% (21/52) from control group (no data for 18/70 pts), p = 0.82. The proportion of R-DA-EPOCH was higher in the upfront group (54% (19/35) R-DA-EPOCH vs 21% (15/70), p = 0.004). No differences were found in other characteristics. Cox proportional hazards model was used to estimate the effects of the prognostic risk factors by univariable and multivariable settings with loss-to-follow-up point censoring. Proportional hazards assumption was verified for all models. Kaplan-Meier method was used to estimate OS and PFS. Log-rank test was used to evaluate differences in survival. A two-sided p-value of <0.05 significance level was considered to be statistically significant in all analyses. Results: Upfront group demonstrated benefit in 3-yr PFS – 91.4% [95% CI 82.6 – 100] vs 71.9% [95% CI 61.9 – 83.6], р = 0.023. The same result was achieved in a multivariable setting (HR = 0.25 [95% CI 0.07 – 0.97], p = 0.035). DEL was the negative prognostic factor (HR = 3.87 [95% CI 1.61 – 9.31], p = 0.003) for 3-yr PFS. Treatment by R-DA-EPOCH only tended to increase 3-yr PFS (HR = 0.3 [95% CI 0.08 – 1.06], p = 0.061). Upfront pts had better 3-yr OS – 97.1% [95% CI 91.8 – 100] vs 75.7% [95% CI 66.3 – 86.5], р = 0.034. In multivariable setting, upfront HDCT with auto-HSCT significantly increased 3-yr OS (HR = 0.2 [95% CI 0.04 – 0.97], p = 0.046). Both early (HR = 144.4 [95% CI 24.2 – 861.4], p < 0,001) and late (HR = 20.8 [95% CI 4.03 – 108], p < 0.001) relapses drastically decreased 3-yr OS. Also, 3-yr OS and PFS were analyzed separately according to the DEL status. In DEL(+) upfront pts 3-yr PFS was 100% [95% CI 100 – 100] vs 28.6% [95% CI 13 – 62.7] in control, p < 0.001. The same impact of upfront in DEL(+) pts was found in 3-yr OS – 100% [95% CI 100 – 100] vs 57.1% [95% CI 39,5 – 82,8] in control, р = 0.002. There was no impact of upfront HDCT with auto-HSCT on 3-yr PFS among DEL(-) pts – 86.4% [95% CI 73.2 – 100] in upfront vs 83.5% [95% CI 71.3 – 97.8] in control, р = 0.71. There was a tendency in improvement of 3-yr OS in upfront group – 95.5% [95% CI 87.1 – 100] vs 77.4% [95% CI 64 – 93.6] in control group, р = 0.11. Summary/Conclusion: 1.Upfront HDCT with auto-HSCT demonstrated a significant benefit in 3-yr PFS (р = 0.023) and OS (р = 0.034). DEL was the negative prognostic factor for 3-yr PFS (р = 0.003). 2.DEL (+) pts had better 3-yr PFS (p < 0.001) and OS (p < 0.001) if treated by upfront HDCT with auto-HSCT. 3.Upfront HDCT with auto-HSCT could serve a clinical option to improve the efficacy in first-line therapy stage IV DLBCL, especially in DEL(+) cases. Keywords: Autologous hematopoietic stem cell transplantation, High risk, Diffuse large B cell lymphoma